Association of PHB 1630 C > T and MTHFR 677 C > T polymorphisms with breast and ovarian cancer risk in BRCA1/2 mutation carriers: results from a multicenter study

A. Jakubowska; C. Jacobs; D. Rozkrut; A. Antoniou; U. Hamann; R. J. Scott; L. McGuffog; S. Healy; O. M. Sinilnikova; G. Rennert; F. Lejbkowicz; A. Flugelman; I. L. Andrulis; G. Glendon; H. Ozcelik; M. Thomassen; M. Paligo; P. Aretini; J. Kantala; B. Aroer; A. Von Wachenfeldt; A. Liljegren; N. Loman; K. Herbst; U. Kristoffersson; R. Rosenquist; P. Karlsson; M. Stenmark-Askmalm; B. Melin; K. L. Nathanson; S. M. Domchek; T. Byrski; T. Huzarski; J. Gronwald; J. Menkiszak; C. Cybulski; P. Serrano; A. Osorio; T. R. Cajal; M. Tsitlaidou; J. Benitez; M. Gilbert; M. Rookus; C. M. Aalfs; I. Kluijt; J. L. Boessenkool-Pape; H. E. J. Meijers-Heijboer; J. C. Oosterwijk; C. J. van Asperen; M. J. Blok; M. R. Nelen; A. M. W. van den Ouweland; C. Seynaeve; R. B. van der Luijt; P. Devilee; D. F. Easton; S. Peock; D. Frost; R. Platte; S. D. Ellis; E. Fineberg; D. G. Evans; F. Lalloo; R. Eeles; J. Adlard; R. Davidson; D. Eccles; T. Cole; J. Cook; A. Godwin; B. Bove; D. Stoppa-Lyonnet; V. Caux-Moncoutier; M. Belotti; C. Tirapo; S. Mazoyer; L. Barjhoux; N. Boutry-Kryza; P. Pujol; I. Coupier; J-P Peyrat; P. Vennin; D. Muller; J-P Fricker; L. Venat-Bouvet; OTh Johannsson; C. Isaacs; R. Schmutzler; B. Wappenschmidt; A. Meindl; N. Arnold; R. Varon-Mateeva; D. Niederacher; C. Sutter; H. Deissler; S. Preisler-Adams; J. Simard; P. Soucy; F. Durocher; G. Chenevix-Trench; J. Beesley; X. Chen; T. Rebbeck; F. Couch; X. Wang; N. Lindor; Z. Fredericksen; V. S. Pankratz; P. Peterlongo; B. Bonanni; S. Fortuzzi; B. Peissel; C. Szabo; P. L. Mai; J. T. Loud; J. Lubinski; KConFab

doi:10.1038/bjc.2012.160

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Association of PHB 1630 C > T and MTHFR 677 C > T polymorphisms with breast and ovarian cancer risk in BRCA1/2 mutation carriers: results from a multicenter study

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Association of PHB 1630 C > T and MTHFR 677 C > T polymorphisms with breast and ovarian cancer risk in BRCA1/2 mutation carriers: results from a multicenter study

A. Jakubowska, C. Jacobs, D. Rozkrut, A. Antoniou, U. Hamann, R. J. Scott, L. McGuffog, S. Healy, O. M. Sinilnikova, G. Rennert, …

British journal of cancer, Vol.106(12), pp.2016-2024

05/06/2012

DOI: https://doi.org/10.1038/bjc.2012.160

PMCID: PMC3388557

PMID: 22669161

Abstract

Life Sciences & Biomedicine

Science & Technology

Oncology

BACKGROUND: The variable penetrance of breast cancer in BRCA1/2 mutation carriers suggests that other genetic or environmental factors modify breast cancer risk. Two genes of special interest are prohibitin (PHB) and methylene-tetrahydrofolate reductase (MTHFR), both of which are important either directly or indirectly in maintaining genomic integrity. METHODS: To evaluate the potential role of genetic variants within PHB and MTHFR in breast and ovarian cancer risk, 4102 BRCA1 and 2093 BRCA2 mutation carriers, and 6211 BRCA1 and 2902 BRCA2 carriers from the Consortium of Investigators of Modifiers of BRCA1 and BRCA2 (CIMBA) were genotyped for the PHB 1630 C>T (rs6917) polymorphism and the MTHFR 677 C>T (rs1801133) polymorphism, respectively. RESULTS: There was no evidence of association between the PHB 1630 C>T and MTHFR 677 C>T polymorphisms with either disease for BRCA1 or BRCA2 mutation carriers when breast and ovarian cancer associations were evaluated separately. Analysis that evaluated associations for breast and ovarian cancer simultaneously showed some evidence that BRCA1 mutation carriers who had the rare homozygote genotype (TT) of the PHB 1630 C>T polymorphism were at increased risk of both breast and ovarian cancer (HR 1.50, 95% CI 1.10-2.04 and HR 2.16, 95% CI 1.24-3.76, respectively). However, there was no evidence of association under a multiplicative model for the effect of each minor allele. CONCLUSION: The PHB 1630TT genotype may modify breast and ovarian cancer risks in BRCA1 mutation carriers. This association need to be evaluated in larger series of BRCA1 mutation carriers. British Journal of Cancer (2012) 106, 2016-2024. doi:10.1038/bjc.2012.160 www.bjcancer.com Published online 15 May 2012 (C) 2012 Cancer Research UK

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Title: Association of PHB 1630 C > T and MTHFR 677 C > T polymorphisms with breast and ovarian cancer risk in BRCA1/2 mutation carriers: results from a multicenter study
Creators: A. Jakubowska - College Station Medical Center
C. Jacobs - Guys & St Thomas NHS Fdn Trust, London, England
D. Rozkrut - University of Szczecin
A. Antoniou - University of Cambridge
U. Hamann - Heidelberg
R. J. Scott - College Station Medical Center
L. McGuffog - University of Cambridge
S. Healy - College Station Medical Center
O. M. Sinilnikova - Ctr Hosp Univ Lyon, Unite Mixte Genet Constitut Canc Frequents, Hosp Civil Lyon, Ctr Leon Berard Lyon, Lyon, France
G. Rennert - Technion – Israel Institute of Technology
F. Lejbkowicz - Technion – Israel Institute of Technology
A. Flugelman - Technion – Israel Institute of Technology
I. L. Andrulis - Canc Care Ontario, Dept Mol Genet, Ontario Canc Genet Network, Toronto, ON, Canada
G. Glendon - Canc Care Ontario, Dept Mol Genet, Ontario Canc Genet Network, Toronto, ON, Canada
H. Ozcelik - Lunenfeld-Tanenbaum Research Institute
M. Thomassen - Odense Univ Hosp, Dept Clin Genet, DK-5000 Odense, Denmark
M. Paligo - Univ Hosp Pisa, Sect Genet Oncol, Pisa, Italy
P. Aretini - Univ Hosp Pisa, Sect Genet Oncol, Pisa, Italy
J. Kantala - Karolinska Univ Hosp, Dept Clin Genet, Stockholm, Sweden
B. Aroer - Karolinska Univ Hosp, Dept Oncol, Stockholm, Sweden
A. Von Wachenfeldt - Karolinska Univ Hosp, Dept Oncol, Stockholm, Sweden
A. Liljegren - Karolinska Univ Hosp, Dept Oncol, Stockholm, Sweden
N. Loman - Univ Lund Hosp, Dept Oncol, S-22185 Lund, Sweden
K. Herbst - Univ Lund Hosp, Dept Oncol, S-22185 Lund, Sweden
U. Kristoffersson - Univ Lund Hosp, Dept Clin Genet, S-22185 Lund, Sweden
R. Rosenquist - Uppsala University
P. Karlsson - Sahlgrens Univ Hosp, Dept Oncol, Gothenburg, Sweden
M. Stenmark-Askmalm - Linköping University
B. Melin - Umeå University
K. L. Nathanson - Supreme Council Of Health
S. M. Domchek - Supreme Council Of Health
T. Byrski - College Station Medical Center
T. Huzarski - College Station Medical Center
J. Gronwald - College Station Medical Center
J. Menkiszak - College Station Medical Center
C. Cybulski - College Station Medical Center
P. Serrano - College Station Medical Center
A. Osorio - Spanish Natl Canc Res Ctr, Human Genet Grp, Madrid, Spain
T. R. Cajal - Hosp Santa Creu & Sant Pau, Oncol Serv, E-08025 Barcelona, Spain
M. Tsitlaidou - National Centre of Scientific Research "Demokritos"
J. Benitez - Spanish Natl Canc Res Ctr, Human Genet Grp, Madrid, Spain
M. Gilbert - Heidelberg
M. Rookus - Netherlands Canc Inst, Dept Epidemiol, Amsterdam, Netherlands
C. M. Aalfs - University of Amsterdam
I. Kluijt - Netherlands Canc Inst, Dept Family Canc Clin, Amsterdam, Netherlands
J. L. Boessenkool-Pape - Netherlands Canc Inst, Dept Epidemiol, Amsterdam, Netherlands
H. E. J. Meijers-Heijboer - University of Amsterdam
J. C. Oosterwijk - University of Groningen
C. J. van Asperen - Leiden University
M. J. Blok - Univ Hosp Maastricht, Dept Clin Genet, Maastricht, Netherlands
M. R. Nelen - Radboud University Nijmegen
A. M. W. van den Ouweland - Erasmus MC, Dept Clin Genet, Family Canc Clin, Rotterdam, Netherlands
C. Seynaeve - Erasmus MC, Dept Med Oncol, Family Canc Clin, Rotterdam, Netherlands
R. B. van der Luijt - College Station Medical Center
P. Devilee - Leiden University
D. F. Easton - University of Cambridge
S. Peock - University of Cambridge
D. Frost - University of Cambridge
R. Platte - University of Cambridge
S. D. Ellis - University of Cambridge
E. Fineberg - University of Cambridge
D. G. Evans - NHS Fdn Trust, Manchester Acad Hlth Sci Ctr, Cent Manchester Univ Hosp, Manchester, Lancs, England
F. Lalloo - NHS Fdn Trust, Manchester Acad Hlth Sci Ctr, Cent Manchester Univ Hosp, Manchester, Lancs, England
R. Eeles - Royal Marsden NHS Fdn Trust, London, England
J. Adlard - Yorkshire Reg Genet Serv, Leeds, W Yorkshire, England
R. Davidson - Yorkhill Hosp, Ferguson Smith Ctr Clin Genet, Glasgow, Lanark, Scotland
D. Eccles - University of Southampton
T. Cole - Birmingham Womens Hosp Healthcare NHS Trust, W Midlands Reg Genet Serv, Birmingham, W Midlands, England
J. Cook - Sheffield Childrens Hosp, Sheffield Clin Genet Serv, Sheffield, S Yorkshire, England
A. Godwin - University of Kansas
B. Bove - Fox Chase Canc Ctr, Clin Mol Genet Lab, Philadelphia, PA 19111 USA
D. Stoppa-Lyonnet - Institute Curie
V. Caux-Moncoutier - Institute Curie
M. Belotti - Institute Curie
C. Tirapo - Institute Curie
S. Mazoyer - Inserm
L. Barjhoux - Inserm
N. Boutry-Kryza - Ctr Hosp Univ Lyon, Unite Mixte Genet Constitut Canc Frequents, Hosp Civil Lyon, Ctr Leon Berard Lyon, Lyon, France
P. Pujol - CHU Arnaud de Villeneuve, Unite Oncogenet, Montpellier, France
I. Coupier - CHU Arnaud de Villeneuve, Unite Oncogenet, Montpellier, France
J-P Peyrat - Ctr Oscar Lambret, Lab Oncol Mol Humaine, F-59020 Lille, France
P. Vennin - Ctr Oscar Lambret, Consultat Oncogenet, F-59020 Lille, France
D. Muller - CLCC Paul Strauss, Unite Oncogenet, Strasbourg, France
J-P Fricker - CLCC Paul Strauss, Unite Oncogenet, Strasbourg, France
L. Venat-Bouvet - College Station Medical Center
OTh Johannsson - National University Hospital of Iceland
C. Isaacs - Georgetown University
R. Schmutzler - Univ Hosp Cologne, Ctr Familial Breast & Ovarian Canc, Dept Obstet & Gynaecol, Cologne, Germany
B. Wappenschmidt - Univ Hosp Cologne, Ctr Familial Breast & Ovarian Canc, Dept Obstet & Gynaecol, Cologne, Germany
A. Meindl - Ludwig Maximilian University of Munich
N. Arnold - Univ Kiel, Dept Obstet & Gynaecol, Univ Hosp Schleswig Holstein, D-24098 Kiel, Germany
R. Varon-Mateeva - Inst Human Genet, Charite Berlin, Germany
D. Niederacher - Univ Dusseldorf, Dept Obstet & Gynaecol, Univ Hosp Dusseldorf, D-40225 Dusseldorf, Germany
C. Sutter - Heidelberg
H. Deissler - Univ Hosp Ulm, Dept Obstet & Gynaecol, Ulm, Germany
S. Preisler-Adams - University of Münster
J. Simard - Univ Laval, Quebec City, PQ, Canada
P. Soucy - Univ Laval, Quebec City, PQ, Canada
F. Durocher - Univ Laval, Quebec City, PQ, Canada
G. Chenevix-Trench - College Station Medical Center
J. Beesley - College Station Medical Center
X. Chen - College Station Medical Center
T. Rebbeck - Univ Penn, Dept Biostat & Epidemiol, Perelman Sch Med, Philadelphia, PA 19104 USA
F. Couch - College Station Medical Center
X. Wang - College Station Medical Center
N. Lindor - College Station Medical Center
Z. Fredericksen - Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA
V. S. Pankratz - Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA
P. Peterlongo - Fdn IRCCS Ist Nazl Tumori INT, Unit Mol Bases Genet Risk & Genet Testing, Dept Prevent & Predicted Med, Milan, Italy
B. Bonanni - Ist Europeo Oncol, Div Canc Prevent & Genet, Milan, Italy
S. Fortuzzi - Fdn Ist FIRC Oncol Mol, IFOM 82, Milan, Italy
B. Peissel - Fdn IRCCS Ist Nazl Tumori INT, Unit Med Genet, Dept Prevent & Prevent Med, Milan, Italy
C. Szabo - College Station Medical Center
P. L. Mai - Dept Hlth & Human Serv, Clin Genet Branch, Div Canc Epidemiol & Genet, NCI,NIH, Rockville, MD 20852 USA
J. T. Loud - Dept Hlth & Human Serv, Clin Genet Branch, Div Canc Epidemiol & Genet, NCI,NIH, Rockville, MD 20852 USA
J. Lubinski - College Station Medical Center
KConFab
Publication Details: British journal of cancer, Vol.106(12), pp.2016-2024
Publisher: Springer Nature
Number of pages: 9
Date published: 05/06/2012
Grant note: Susan G Komen Foundation Basic, Clinical and Translational 12051203 / Ghent university; Ghent University Susan G Komen Foundation; Susan G. Komen Breast Cancer Foundation NF-SI-0510-10096 / National Institute for Health Research; National Institute for Health Research (NIHR) 301/08/P103 / Grant Agency of the Czech republic; Grant Agency of the Czech Republic; Norwegian Agency for Development Cooperation - NORAD 1.5.150.07 / Fund for Scientific Research Flanders (FWO); FWO 10118; 11022; 15007 / Cancer Research UK Breast Cancer Research Foundation Cancer Care Ontario, Canada (ILA) RFA-CA-06-503 / National Cancer Institute, National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) Mayo Rochester Early Career Development Award for Non-Clinician Scientists Istituto Toscano Tumori -MZ0 MOU 2005 / Ministry of Health of the CR
Identifiers: 99822262802346
Academic Unit: School of Health Sciences
Language: English
Resource Type: Journal article

Association of PHB 1630 C > T and MTHFR 677 C > T polymorphisms with breast and ovarian cancer risk in BRCA1/2 mutation carriers: results from a multicenter study

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